The benzodiazepine drug is widely clinically used for antianxiety, sedation and hypnosis. As the first water-soluble benzodiazepine derivative, midazolam has been widely used in clinical sedation, hypnosis, analgesia, antiepileptic, antianxiety and general anesthesia. When midazolam is infused as anesthetic into human body, it could be oxidized into α-hydroxyl-midazolam by cytochrome P450 3A4 isoenzyme. The oxidative product still has pharmacological activity, thereby inducing a long time of anesthetic effect and a slow waking up. According, it is desired for pharmaceutical chemists to develop a novel benzodiazepine water-soluble derivative with faster induction time of anesthesia and shorter maintenance time.
In 1999, remimazolam (CNS7056, formula (III)) has been designed and synthesized by GlaxoSmithKline:

It attracted great attention in the pharmaceutical industry for the short induction time, low incidence of respiratory depression and short consciousness recovery time. In the sedative clinical trial II of 49 ICU patients in 2013, however, five patients were found to have prolonged waking up time. Five patients have higher serum concentration of remimazolam but the reason was unknown (http://www.paion.de/images/stories/investoren/finanznachrichten/2014/en/japantelco.pdf). The development was terminated by ONO PHARMACEUTICAL CO., LTD due to unclarity of the metabolism in 2014.
The present inventors designed and synthesized a novel water-soluble benzodiazepine derivative to solve the problem in the prior art, which has lower toxicity after metabolism in vivo and has the advantages of fast action, short maintaining time and rapid recovery.